Pyridine → Benzhydryl 7-amino-3-cephem-4-carboxylate

HRID 1905806Notes

Reaction equation

HRID 1905806 reaction equation
[C:1]1([CH:7]([O:14][C:15]([CH:17]2[N:22]3[C:23](=[O:35])[C@@H:24]([NH:25]C(=O)CC4C=CC=CC=4)[C@H:21]3[S:20][CH2:19][CH:18]2OS(C)(=O)=O)=[O:16])[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.N1C=CC=CC=1.P(Cl)(Cl)(Cl)(Cl)Cl.C(N(CC)CC)C>ClCCl.CO>[C:1]1([CH:7]([O:14][C:15]([C:17]2[N:22]3[C:23](=[O:35])[CH:24]([NH2:25])[C@H:21]3[S:20][CH2:19][CH:18]=2)=[O:16])[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

7

Reactant 4

HCID 1049PyridineHCID 8471TriethylamineHCID 24819Phosphorus pentachlorideHCID 137854843-Methanesulfonyloxy-7beta-phenylacetylaminocepham-4-carboxylic acid diphenylmethyl ester

Product 1

HCID 12098365Benzhydryl 7-amino-3-cephem-4-carboxylateYield 55.7%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-30 °C

Procedure

To a solution of 3-methanesulfonyloxy-7beta-phenylacetylaminocepham-4-carboxylic acid diphenylmethyl ester (3c) in dichloromethane (7 parts) cooling at -25° to -20° C. under nitrogen are added pyridine (2 equivalents) and phosphorus pentachloride (1.7 equivalents). After stirring at -15° to -10° C. for 4 hours, the mixture is diluted with methanol (12 parts) cooled at -40° to -30° C. After stirring for 30 minutes at -30° C. and for 2.5 hours at 0° to 5° C., the mixture is cooled to -30° C., mixed dropwise with triethylamine (8.1 equivalents) and let stand overnight at 0° to 5° C. The mixture is diluted with dichloromethane and ice-water and stirred for 20 minutes at 0° to 5° C. The formed organic layer is taken, washed with hydrochloric acid, water, aqueous sodium hydrogen carbonate, and water, dried, and concentrated. The residue is crystallized from ethyl acetate to give 7beta-amino-3-cephem-4-carboxylic acid diphenylmethyl ester (5). Yield: 55.7%.

Workup

  1. temperaturecooled at -40° to -30° C
  2. stirringAfter stirring for 30 minutes at -30° C. and for 2.5 hours at 0° to 5° C.
  3. waitlet stand overnight at 0° to 5° C
  4. stirringstirred for 20 minutes at 0° to 5° C
  5. washwashed with hydrochloric acid, water, aqueous sodium hydrogen carbonate, and water
  6. customdried
  7. concentrationconcentrated
  8. customThe residue is crystallized from ethyl acetate

Sources & evidence

ORD record
ord-862ab793ead84144b84afbda5d94f8d3
Source dataset
uspto-grants-1987_03
Patent number
US04647658

Reaction notes

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